Skeletal accumulation of fluorescently tagged zoledronate is higher in animals with early stage chronic kidney disease.
Citation | Swallow, E A, et al. “Skeletal Accumulation of Fluorescently Tagged Zoledronate Is Higher in Animals With Early Stage Chronic Kidney Disease”. 2018. Osteoporosis International : A Journal Established As Result of Cooperation Between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, vol. 29, no. 9, 2018, pp. 2139–2146. |
Center | Indiana University |
Author | E A Swallow, M W Aref, N Chen, I Byiringiro, M A Hammond, B P McCarthy, P R Territo, M M Kamocka, S Winfree, K W Dunn, S M Moe, M R Allen |
Keywords | Bisphosphonate, bone, CKD, Drug accumulation |
Abstract |
This work examines the skeletal accumulation of fluorescently tagged zoledronate in an animal model of chronic kidney disease. The results show higher accumulation in 24-h post-dose animals with lower kidney function due to greater amounts of binding at individual surfaces. INTRODUCTION: Chronic kidney disease (CKD) patients suffer from increased rates of skeletal-related mortality from changes driven by biochemical abnormalities. Bisphosphonates are commonly used in reducing fracture risk in a variety of diseases, yet their use is not recommended in advanced stages of CKD. This study aimed to characterize the accumulation of a single dose of fluorescently tagged zoledronate (FAM-ZOL) in the setting of reduced kidney function. METHODS: At 25 weeks of age, FAM-ZOL was administered to normal and CKD rats. Twenty-four hours later, multiple bones were collected and assessed using bulk fluorescence imaging, two-photon imaging, and dynamic histomorphometry. RESULTS: CKD animals had significantly higher levels of FAM-ZOL accumulation in the proximal tibia, radius, and ulna, but not in lumbar vertebral body or mandible, based on multiple measurement modalities. Although a majority of trabecular bone surfaces were covered with FAM-ZOL in both normal and CKD animals, the latter had significantly higher levels of fluorescence per unit bone surface in the proximal tibia. CONCLUSIONS: These results provide new data regarding how reduced kidney function affects drug accumulation in rat bone. |
Year of Publication |
2018
|
Journal |
Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA
|
Volume |
29
|
Issue |
9
|
Number of Pages |
2139-2146
|
Date Published |
09/2018
|
ISSN Number |
1433-2965
|
DOI |
10.1007/s00198-018-4589-3
|
Alternate Journal |
Osteoporos Int
|
PMID |
29947866
|
PMCID |
PMC6103914
|
Download citation |